Patent NZ-501293-A (NZ)
Title: 1H-imidazole-4-ylmethylquinoline derivatives, useful as inhibitors of farnesyl protein transferase or prenyl transferase or for treating tumours or autoimmune diseases
Inventor: BHIDE RAJEEV S
IPC: A61K31/55
Filed: 1998-06-16
Abstract: The compound has the formula I, wherein: I is 0, m is 1, n is 1; r, s and t are 0 or 1; Y is CHR12, SO2, SO3, CO, CO2, O, NR13, SO2NR14, CONR15, C(NCN), C(NCN)NR16, NR17CO, NR18SO2, CONR19NR20, SO2NR21NR22, S(O)(NR23), or S(NR24)(NR25), or Y is absent; Z is CR12, S, SO, SO2, SO3, CO, CO2, O, NR13, SO2NR14, CONR15, NR26NR27, ONR28, NR29O, NR30SO2NR31, NR32SO2, NR33C(NCN), NR34C(NCN)NR35, NR36CO, NR37CONR38, NR39CO2, OCONR40, S(O)(NR41), S(NR42)(NR43) or CHR12; or Z is absent; R7, R8 are H, halo, nitro, cyano or U-R44; U is selected from the group consisting of S, O, NR45, CO, SO, SO2, CO2, NR46CO2, NR47CONR48, NR49SO2, NR50SO2NR51, SO2NR52, NR53CO, CONR54, PO2R55 or PO3R56 or U is absent; R9, R10, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58 and R59 are H, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl; R11 and R44 are H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, or substituted heterocyclo; R1, R2, R3, R4, R5 and R6 are H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are H, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo; any two of R1, R2, R3, R4, R5 and R6 can join to form a cycloalkyl group; any two of R1, R2, R3, R4, R5 and R6 together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are CH2, CO and CH(CH2)pQ wherein Q is NR57R58, OR59 or CN; wherein p is 0, 1 or 2; and A, B and C are carbon, oxygen, sulfur or nitrogen; D is carbon, oxygen, sulfur or nitrogen or D is absent; its enantiomers, diastereomers, pharmaceutically acceptable salts, prod rug and solvates thereof; with the provisos that: R11 may be H except when Z is SO, or when Z is O, NR13 or S and the carbon to which it is attached is part of a double bond or when Y is SO2, CO2, NR18SO2, S(O)(NR23), or S(NR24)(NR25); and R44 may be hydrogen except when U is SO, SO2, NR46CO2 or NR49SO2. A pharmaceutical composition comprising the compound of formula I is also described. The compounds of formula I are used for inhibiting farnesyl protein transferase, for inhibiting prenyl transferases, for inhibiting tumours and for treating diseases associated with signal transduction pathways operating through ras. The compounds of formula I are also used for treating diseases that are associated with proteins that are post-translationally modified by the enzyme farnesyl protein transferase or by the enzyme geranylgeranyl protein transferase. The compounds of formula I are also used for treating autoimmune diseases.